Betulinic acid protects against LPS-induced intestinal inflammatory damage via inhibiting Nrf2/TXNIP/NLRP3 signaling pathways in mice

Betulinic acid (BA) is a pentacyclic triterpenoid and found in various fruits and vegetables, known for its anti-inflammatory and antioxidant properties as well as intestinal protective roles. This study aimed to investigate the effects and mechanisms of BA on lipopolysaccharide (LPS)-induced intestinal inflammation in mice. Our results indicated that BA pretreatment alleviated LPS-induced body weight loss, morphological damage and intestinal cell apoptosis in the duodenum, jejunum, ileum and colon. BA pretreatment effectively regulated the disturbance of inflammatory cytokines in the duodenum, jejunum, ileum and colon induced by LPS. Meanwhile, BA pretreatment significantly inhibited the protein expression of TXNIP, NLRP3, ASC, caspase-1, GSDMD, IL-1β and IL-18 in the jejunum, suggesting that BA mitigated LPS-induced intestinal inflammation by inhibiting the TXNIP/NLRP3 signaling pathways. Furthermore, BA pretreatment decreased MDA content, while increasing the activities of the CAT and SOD in the jejunum. Subsequently, BA pretreatment down-regulated the protein expression of Nrf2 and HO-1 in the jejunum, indicating that BA alleviated LPS-induced intestinal oxidative impairment by inhibiting the Nrf2 signaling pathway. In conclusion, BA pretreatment exhibited protective effects on LPS-induced intestinal inflammatory damage by inhibiting Nrf2/TXNIP/NLRP3 signaling pathways in mice. This study established a theoretical foundation for the application of BA as a functional food factor in the alleviation of inflammatory bowel diseases.